Abstract 2663
Background
The NOD2 agonist muramyl-dipeptide (MDP), a peptidoglycan motif common to all bacteria, supports LGR5+ intestinal stem cells (ISCs) survival through NOD2 activation upon an otherwise lethal oxidative-stress-mediated signal. Yet the underlying protective mechanisms remains unknown.
Methods
Irradiation was used as stressor and primarily murine-derived intestinal organoids as a model system.
Results
MDP induced a strong reduction of total and mitochondrial reactive oxygen species (ROS) within ISCs, which was associated with mitophagy induction. ATG16L1 KO and NOD2 KO organoids did not benefit from the MDP-induced cytoprotection. We showed the MDP-dependent induction of ISC mitophagy upon stress in vivo.
Conclusions
In LGR5+ ISCs, NOD2 allows irradiation-generated ROS clearance through ATG16L1-activated mitophagy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work was supported by European Research Council (ERC) advanced grant 339579-DECRYPT to P.J.S and by French National Research Agency (ANR) grant 17-CE14-0022 (i-Stress) to P.S.. A.L. was personally funded by: i) Poste d’Accueil INSERM and ii) Soutien pour la formation à la recherche translationnelle en cancérologie (ITMO Cancer, INCa - Plan Cancer 2014-2019, allocation number: ASC17040JSA).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3157 - Efficacy and safety of anlotinib in advanced leiomyosarcoma: Subgroup analysis of a phase IIB trial (ALTER0203)
Presenter: Yihebali Chi
Session: Poster Display session 1
Resources:
Abstract
3710 - The effect of treatment line on the efficacy of Anlotinib hydrochloride in advanced alveolar soft part sarcoma patients
Presenter: Zhiwei Fang
Session: Poster Display session 1
Resources:
Abstract
3184 - Prior exposure to pazopanib (PAZ) did not minor efficacy of regorafenib (REG) in non-adipocytic soft tissue sarcoma patients (pts)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
798 - Pexidartinib (Pex) for locally advanced tenosynovial giant cell tumor (TGCT): characterization of hepatic adverse reactions (ARs)
Presenter: Sebastian Bauer
Session: Poster Display session 1
Resources:
Abstract
6117 - VEGFR2 and ITGA polymorphisms as novel pan-sarcoma biomarkers for sensitivity prediction as well as toxicity prevention anti-angiogenesis therapy in pediatric and young adult
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
5450 - Reversion of resistance to mTOR inhibitors with the addition of exemestane in patients with malignant PEComa.
Presenter: Roberta Sanfilippo
Session: Poster Display session 1
Resources:
Abstract
4279 - Efficacy and Safety of VEGFR2 Inhibitor Apatinib combined with chemotherapy for Sarcoma in Stage IV
Presenter: Zhiwu Ren
Session: Poster Display session 1
Resources:
Abstract
5929 - Outcomes of metastatic soft tissue sarcoma treated with Pazopanib from dedicated medical oncology sarcoma clinic: A holistic care approach from a developing country
Presenter: Akhil Kapoor
Session: Poster Display session 1
Resources:
Abstract
2469 - Inhibition of mTOR signaling enhances Trabectedin activity in Soft Tissue Sarcoma
Presenter: David Moura
Session: Poster Display session 1
Resources:
Abstract
4210 - Efficacy and safety of apatinib for advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib: An open-label, multicenter, single-arm, phase II trial
Presenter: Zhaolun Cai
Session: Poster Display session 1
Resources:
Abstract